The present invention is directed to substituted chromans of the formula (I), depicted below, which by inhibiting 5-lipoxygenase enzyme are useful in the prevention or treatment of asthma, arthritis, psoriasis, ulcers, myocardial infarction, stroke and related disease states in mammals. The present invention is also directed to pharmaceutical compositions, and to a method of treatment
Kreft et al., in U.S. Pat. No. 4,661,596, describe compounds which are disubstituted naphthalenes, dihydronaphthalenes or tetralins having the formula ##STR1## wherein the dotted lines represent optional double bonds, R is 2-pyridyl, 2-quinolyl, 2-pyrazinyl, 2-quinoxalinyl, 2-thiazolyl, 2-benzothiazolyl, 2-oxazolyl, 2-benzoxazolyl, 1-alkyl-2-imidazolyl or 1-alkyl-2-benzimidazolyl and R is hydroxy, lower alkoxy, lower alkyl or perfluoro alkyl. These compounds inhibit lipoxygenase enzyme and antagonize the effects of leukotriene D4, and so are useful in the prevention and treatment of asthma.
Eggler et al., in copending International application PCT/US87/02745 filed Oct. 19, 1987 have described similarly active compounds, including chromans of the formula ##STR2## wherein R.sup.x is substantially defined as above, R.sup.z is aryl or heteroaryl, X.sup.a is, for example, oxygen or CH.sub.2, and X.sup.b is C.dbd.O or CHOH. The present compounds generally fail to block leukotriene D4 receptors and so, in this respect, are differentiated from the compounds of Eggler et al., who also report certain structurally related compounds as intermediates (for example, compounds of the formula immediately above wherein R.sup.x is benzyl Many of these intermediates also find utility as intermediates in the present invention.
The chemical nomenclature employed herein generally follows that of "I.U.P.A.C Nomenclature of Organic Chemistry, 1979 Edition," Pergammon Press, New York, 1979.